Disease-Toxicant Interactions in Manganese Exposed Huntington Disease Mice: Early Changes in Striatal Neuron Morphology and Dopamine Metabolism

YAC128 Huntington's disease (HD) transgenic mice accumulate less manganese (Mn) in the striatum relative to wild-type (WT) littermates. We hypothesized that Mn and mutant Huntingtin (HTT) would exhibit gene-environment interactions at the level of neurochemistry and neuronal morphology. Twelve-week-old WT and YAC128 mice were exposed to MnCl2-4H2O (50 mg/kg) on days 0, 3 and 6. Striatal medium spiny neuron (MSN) morphology, as well as levels of dopamine (DA) and its metabolites (which are known to be sensitive to Mn-exposure), were analyzed at 13 weeks (7 days from initial exposure) and 16 weeks (28 days from initial exposure). No genotype-dependent differences in MSN morphology were apparent at 13 weeks. But at 16 weeks, a genotype effect was observed in YAC128 mice, manifested by an absence of the wild-type age-dependent increase in dendritic length and branching complexity. In addition, genotype-exposure interaction effects were observed for dendritic complexity measures as a function of distance from the soma, where only YAC128 mice were sensitive to Mn exposure. Furthermore, striatal DA levels were unaltered at 13 weeks by genotype or Mn exposure, but at 16 weeks, both Mn exposure and the HD genotype were associated with quantitatively similar reductions in DA and its metabolites. Interestingly, Mn exposure of YAC128 mice did not further decrease DA or its metabolites versus YAC128 vehicle exposed or Mn exposed WT mice. Taken together, these results demonstrate Mn-HD disease-toxicant interactions at the onset of striatal dendritic neuropathology in YAC128 mice. Our results identify the earliest pathological change in striatum of YAC128 mice as being between 13 to 16 weeks. Finally, we show that mutant HTT suppresses some Mn-dependent changes, such as decreased DA levels, while it exacerbates others, such as dendritic pathology

Early Warning Signals of Social Transformation: A Case Study from the US Southwest

abstract: Recent research in ecology suggests that generic indicators, referred to as early warning signals (EWS), may occur before significant transformations, both critical and non-critical, in complex systems. Up to this point, research on EWS has largely focused on simple models and controlled experiments in ecology and climate science. When humans are considered in these arenas they are invariably seen as external sources of disturbance or management. In this article we explore ways to include societal components of socio-ecological systems directly in EWS analysis. Given the growing archaeological literature on ‘collapses,’ or transformations, in social systems, we investigate whether any early warning signals are apparent in the archaeological records of the build-up to two contemporaneous cases of social transformation in the prehistoric US Southwest, Mesa Verde and Zuni. The social transformations in these two cases differ in scope and severity, thus allowing us to explore the contexts under which warning signals may (or may not) emerge. In both cases our results show increasing variance in settlement size before the transformation, but increasing variance in social institutions only before the critical transformation in Mesa Verde. In the Zuni case, social institutions appear to have managed the process of significant social change. We conclude that variance is of broad relevance in anticipating social change, and the capacity of social institutions to mitigate transformation is critical to consider in EWS research on socio-ecological systems.The article is published at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.016368

Circadian regulation of hormone signaling and plant physiology

The survival and reproduction of plants depend on their ability to cope with a wide range of daily and seasonal environmental fluctuations during their life cycle. Phytohormones are plant growth regulators that are involved in almost every aspect of growth and development as well as plant adaptation to myriad abiotic and biotic conditions. The circadian clock, an endogenous and cell-autonomous biological timekeeper that produces rhythmic outputs with close to 24-h rhythms, provides an adaptive advantage by synchronizing plant physiological and metabolic processes to the external environment. The circadian clock regulates phytohormone biosynthesis and signaling pathways to generate daily rhythms in hormone activity that fine-tune a range of plant processes, enhancing adaptation to local conditions. This review explores our current understanding of the interplay between the circadian clock and hormone signaling pathways

An Overview of Thrombophilia and Associated Laboratory Testing

Venous thromboembolism, usually entailing deep vein thrombosis, pulmonary embolism, or both, is a complex and multifactorial disorder, in which a number of putative conditions interplay and finally contribute to propel the individual risk over a certain degree, so ultimately culminating in the development of venous occlusive disorders. Thrombophilia is commonly defined as a propensity to develop venous thromboembolism on the basis of an underlying hypercoagulable state attributable to inherited or acquired disorders of blood coagulation or fibrinolysis. The thrombophilic conditions are conventionally classified as inherited (or genetically determined) and acquired. The former include deficiencies of natural anticoagulants such as antithrombin, protein C, protein S, increased values of clotting factors (especially factor VIII), as well as prothrombotic polymorphisms in genes encoding for factor V (i.e., factor V Leiden) and prothrombin. The latter conditions mainly entail antiphospholipid antibody syndrome, malignancy, acquired elevations of coagulation factors or acquired reduction of natural inhibitors, or hyperhomocysteinemia. Deepened knowledge of all potential risk factors, as well as the clear understanding of their role in the pathophysiology of venous thrombosis, are both essential to help achieve a faster and more efficient diagnosis of this condition as well as a more effective prophylaxis of patients at higher risk and treatment of those with manifest disease